UPLC-LTQ-Orbitrap Study on Rat Urinary Metabolites of 5-Methoxy-Alpha-Methyltryptamine.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2024-01-01 DOI:10.2174/0113892002295551240628061732

Guo Zhutao, Keran Ding, Shuiqing Zheng, Chunfang Ni, Chen Liang, Siyang He, Qianya Deng

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Abstract

Objective: 5-Methoxy-α-Methyltryptamine (5-MeO-AMT) is a new psychoactive substance which is abused due to its hallucinogenic and euphoric effects. This study aimed to study the metabolic characteristics of 5-MeO-AMT.

Methods: Five rats were given intraperitoneal injection at a dose of 50 mg/kg of 5-MeO-AMT, and their urine was subsequently collected at different times within 7 days. Ultra-high performance liquid chromatographytandem high-resolution mass spectrometry (UPLC-LTQ-Orbitrap) was used to detect the precise molecular weight and fragment ions of 5-MeO-AMT and its possible metabolites in the urine sample extracted with benzene-ethyl acetate.

Results: Three metabolites, including OH-5-MeO-AMT, α-Me-5-HT, and N-Acetyl-5-MeO-AMT were identified in rats' urine. The major metabolic pathways involved O-demethylation, hydroxylation of indole ring, and Acetylation on aliphatic amines.

Conclusion: The results of this study are an important reference for the identification and screening of toxicants of 5-MeO-AMT.

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大鼠尿液中 5-甲氧基-Alpha-甲基色胺代谢物的 UPLC-LTQ-Orbitrap 研究

目的：5-甲氧基-α-甲基色胺（5-MeO-AMT）是一种新型精神活性物质，因具有致幻和兴奋作用而被滥用。本研究旨在研究 5-MeO-AMT 的代谢特征：方法：按每公斤 50 毫克的剂量给五只大鼠腹腔注射 5-MeO-AMT，然后在七天内的不同时间收集它们的尿液。采用超高效液相色谱-串联高分辨质谱（UPLC-LTQ-Orbitrap）检测用乙酸苯乙酯提取的尿样中5-MeO-AMT及其可能代谢物的精确分子量和碎片离子：结果：在大鼠尿液中发现了三种代谢物，包括 OH-5-MeO-AMT、α-Me-5-HT 和 N-乙酰基-5-MeO-AMT。主要代谢途径包括 O-脱甲基化、吲哚环羟基化和脂肪胺乙酰化：本研究的结果对识别和筛选 5-MeO-AMT 的毒物具有重要的参考价值。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.